FDA Issues Guidance on Generic Abuse-Deterrent Opioid Development

JANUARY 22, 2018
Jennifer Barrett
FDA officials have released guidance on the development of generic abuse-deterrent opioids. The final guidance is part of the FDA’s effort to reduce abuse by decreasing unnecessary exposure to opioids.

In an FDA statement, Commissioner Scott Gottlieb, MD, said that increasing generic access is key to transitioning from a market dominated by conventional opioids to abuse-deterrent formulations (ADFs).1

“We must have the potential to improve access to the newer formulations, for appropriately selected and monitored patients, through the introduction of generic competitors,” he said.1

The released guidance is intended to assist the industry in its development of generic versions of approved opioids with ADFs by clarifying the FDA’s expectations prior to application submission, in order to reduce time to approval. As part of the guidance, the FDA is providing new recommendations about the type of studies that companies should conduct to demonstrate that their generic drug is no less abuse deterrent than its brand name counterpart.2

According to the statement, FDA officials have approved 10 opioids with ADFs to date: Arymo ER, Embeda, Hysingla ER, MorphaBond ER, OxyContin, RoxyBond, Targiniq ER, Troxyca ER, Xtampza ER, and Vantrela ER. Dr. Gottlieb said that improved access to generic versions of these products could increase uptake by reducing barriers of cost.

According to the guideline, the FDA recommends 6 general principles for developing and evaluating the abuse deterrence of generic solid oral opioid drug products compared with their brand name counterparts2 :
  • Evaluate abuse deterrence using a tier-based approach to testing based on varying levels of complexity, difficulty, and effort that may be used by the abuser to release the opioid drug substance. •
  • Evaluate the abuse deterrence for each potential route of abuse compared with the abuse deterrence of the reference product for that route.
  • Identify the most effective manipulation conditions for both the reference and test products before comparing them.
  • Sample an appropriate amount of the opioids before conducting comparative in vitro studies.
  • Compare test and reference products in extraction studies to assess the vulnerabilities of both products.
  • Statistically compare test and reference products.

The FDA is taking steps to expedite the process of getting ADFs to market by developing improved testing methodologies for evaluating complex features, such as abuse deterrence, for both brand name and generic opioid drug products. Other efforts include the development of new tools for speeding up the generic development of complex products. In addition, the FDA is focusing on improving the evaluation efforts of abuse-deterrent products in the real-world setting, as well as the attitudes and beliefs of health care providers and those who are prescribed these products.

The intention of the new guidance is to decrease addiction rates and prevent unnecessary use of opioids by balancing the need to effectively treat pain with the public health emergency related to opioid abuse, Dr. Gottlieb said. “This is an effort designed to encourage the shift—only when opioids are clinically appropriate—from existing easily abused products to those that are harder to manipulate,” he said.1

  1. Statement from FDA Commissioner Scott Gottlieb, M.D., on steps to promote development of generic versions of opioids formulated to deter abuse [news release]. Silver Spring, MD; FDA; November 21, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm586117.htm. Accessed November 21, 2017.
  2. US Department of Health and Human Services; FDA; Center for Drug Evaluation and Research. General principles for evaluating the abuse deterrence of generic solid oral opioid drug products: guidance for industry. FDA website. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ UCM492172. Published November 2017. Accessed November 21, 2017.